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Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT.

AbstractBACKGROUND:
Statins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP); addition of ezetimibe to statins further reduces LDL-C and hs-CRP. An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).
METHODS AND RESULTS:
The IMPROVE-IT trial randomly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin. LDL-C and hs-CRP were measured at baseline and 1 month after randomization. Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target, adjusting for differences in baseline characteristics. An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline, with no 1-month values, or with end points before 1 month were excluded. Of 15 179 patients, 39% achieved the dual LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) targets at 1 month, 14% met neither target, 14% met only the hs-CRP target, and 33% met only the LDL-C target. Those achieving dual targets had lower primary end point rates than those meeting neither target (cardiovascular death, major coronary event, or stroke; 38.9% versus 28.0%; adjusted hazard ratio, 0.73; 0.66-0.81; P<0.001). More patients treated with ezetimibe/simvastatin met dual targets than those treated with simvastatin alone (50% versus 29%, P<0.001). The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment (P-interaction=0.65). Similar findings were observed using the exploratory targets.
CONCLUSIONS:
Significantly more patients treated with ezetimibe/simvastatin met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone. Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment.
CLINICAL TRIAL REGISTRATION:
URL: http://www.clinicaltrials.gov; Unique identifier: NCT00202878.
AuthorsErin A Bohula, Robert P Giugliano, Christopher P Cannon, Jing Zhou, Sabina A Murphy, Jennifer A White, Andrew M Tershakovec, Michael A Blazing, Eugene Braunwald
JournalCirculation (Circulation) Vol. 132 Issue 13 Pg. 1224-33 (Sep 29 2015) ISSN: 1524-4539 [Electronic] United States
PMID26330412 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright© 2015 American Heart Association, Inc.
Chemical References
  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • C-Reactive Protein
  • Simvastatin
  • Creatinine
  • Ezetimibe
Topics
  • Acute Coronary Syndrome (blood, drug therapy)
  • Aged
  • Anticholesteremic Agents (administration & dosage, therapeutic use)
  • Biomarkers
  • C-Reactive Protein (analysis)
  • Cardiovascular Diseases (mortality)
  • Cerebral Revascularization
  • Cholesterol, LDL (blood)
  • Comorbidity
  • Creatinine (blood)
  • Double-Blind Method
  • Drug Monitoring
  • Drug Therapy, Combination
  • Electrocardiography
  • Ezetimibe (administration & dosage, therapeutic use)
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, therapeutic use)
  • Male
  • Middle Aged
  • Myocardial Infarction (blood, drug therapy)
  • Myocardial Revascularization
  • Simvastatin (administration & dosage, therapeutic use)
  • Treatment Outcome

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